Bone is a dynamic tissue which undergoes cellular remodeling throughout like. The remodeling is probably initiated by the generation of locally acting factors capable of inducing osteoclastic bone resorption and is completed with the formation of new bone. It is thought that the stimulus for new bone formation is triggered by the resorption process (i.e. bone resorption causes the release of factors capable of stimulating bone formation). Bone formation is accomplished by osteoblasts and is thought to include the following process: chemotaxis of osteoblast precursors to the site of resorption, proliferation of these precursors, their differentiation to mature osteoblasts, and the subsequent synthesis of extracellular matrix including collagen. The goal of this project is to examine the factors which may couple bone resorption with bone formation by studying these events in vitro and in vivo. In order to accomplish this, we will examine the ability of growth factors (PDGF, FGF, EGF, IL-1, IGF- 1 and TGF-Beta) to modulate alkaline phosphatase activity, osteocalcin, protein, collagen and DNA synthesis and cellular proliferation and chemotaxis of bone cells in vitro. Once these events are defined for well characterized growth factors we will study the ability of serum free medium conditioned by resorbing bone organ cultures to stimulate similar events. The response of the conditioned medium will then be compared with the response of the defined growth factors. By use of radio receptor assays, immunochemical assays and by partial purification, the identity of growth factors present in bone organ conditioned medium will be examined. And finally, both well characterized growth factors and concentrated serum free medium conditioned by bone organ cultures will be tested for enhancing bone formation in vivo.